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Nitric oxide (NO) has been highlighted as a key gaseous signaling molecule in the body, playing a central role in various physiological and pathological processes. However, a comprehensive analysis of NO metabolism dynamics in living cells remains a significant challenge. To address this, we have developed and characterized a novel genetically encoded NO fluorescence sensor, GefiNO, to investigate NO metabolism dynamics in living cells and subcellular organelles. In the study, we described the protein detection capabilities and subcellular spatiotemporal localization of GefiNO sensors. By analyzing NO metabolic responses in macrophages of different subtypes, we provide a comprehensive view of NO dynamics at the cellular level. The GefiNO sensor represents a valuable tool for monitoring extensive NO dynamics in living cells and offers potential for uncovering new insights into cellular metabolic mechanisms., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2025 Elsevier Inc. All rights reserved.)

In recent years, the origin and safety of counterfeit meat products have raised significant concerns among consumers. Therefore, there was an urgent need to develop a new method using fingerprinting techniques for meat product traceability. This study aimed to evaluate the traceability and authenticity of beef from Inner Mongolia by measuring the δ 13 C and δ 15 N values, as well as 13 mineral elements. In the complex environment of feeding regimes and agricultural types, δ 15 N, δ 13 C, and Se were selected as characteristic variables to differentiate feeding regimes, while Fe, K, Tl, Sr, Mn, and δ 13 C were chosen as characteristic variables for tracing the origin of the beef. Linear discriminant analysis achieved an accuracy rate of up to 100 %. This research confirmed the effectiveness of combining stable isotopes with mineral elements in accurately determining the origin of Inner Mongolian beef and verifying the authenticity of typical feed, providing a valuable strategy for traceability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nonlinear photoacoustic microscopy (PAM) usually requires dual-pulse excitation. Current approaches to realize dual-pulse laser train are indirect, mainly based on beam combinations. Here, we report a compact (∼5-cm-long cavity) laser source that directly outputs controllable nanosecond (∼34 ns) dual pulses, including the tunability of repetition rate (0-20 kHz), time delay (5-30 µs), and relative intensity ratio (20-500%), perfectly matching the requirements of nonlinear imaging in PAM. The single pulse energy is achieved up to ∼95 µJ. We showcase the nonlinear PA performance with this laser source in typical Grüneisen-relaxation-based applications with imaging contrast enhanced by 8 dB. The promising performance indicates that this dual-pulse laser can readily be applied to nonlinear PAMs, especially for portable applications.

Theoretical investigations using density functional theory (DFT) and ab initio wavefunction theory (WFT) have been performed to understand the geometric and electronic structures, chemical bonding, and structural transformation of 5d x 6s 2 -metal doped triboron clusters MB 3 (M = La, Ta, Re, Ir; x = 1, 3, 5, 7). Global-minimum structural searches find that early-metal doped MB 3 (M = La, Ta) clusters adopt a two-dimensional (2D) planar structure, with σ- and π-type delocalized molecular orbitals (MOs) consisting of M-5d and B-2p atomic orbitals (AOs) identified by chemical bonding analysis. In contrast, late-metal doped MB 3 (M = Re, Ir) clusters prefer three-dimensional (3D) structures of near-pyramidal and triangular pyramid geometries, respectively, which exhibit enhanced stability involving σ- and δ-type M(5d)-B(2p) interactions. The M-B bonding in the Re and Ir borides is more covalent than the La and Ta ones due to less charge transfer and similar orbital energies of late 5d-metals and boron. Moreover, the Jahn-Teller effect leads to MO mixing and electron redistribution, thus enlarging the HOMO-LUMO gaps. This work provides insights into the nature of the structural stability in triboron clusters induced by metal doping.

This study presents an investigation into the electron beam damage phenomenon of Co 3 O 4 under transmission electron microscopy (TEM). It was found that after irradiation at a dose rate of 6.78 × 10 6 e/nm 2 s, Co 3 O 4 crystals exhibited surface reconstruction and faceting features. Electron energy loss spectroscopy (EELS) analysis indicates that the damage process initiates with the desorption of oxygen anions, which subsequently leads to a reduction in the valence state of cobalt cations and corresponding atomic rearrangement. High resolution TEM (HRTEM) reveals that surface faceting, which has an epitaxial relationship with the bulk, could help maintain the crystal lattice of face-centered cubic (fcc) Co 3 O 4 despite Co-O bond breakage upon beam exposure. With a finely focused electron beam, the hole drilling effect was observed. The structural degradation is proposed to arise from inelastic damage that induced partial desorption of oxygen anions and rearrangement of valence-reduced cobalt cations to epitaxially grow on the surface, suggesting an interplay between irradiation damage and material restructuring. The relative phase stability of Co 3 O 4 , combined with its interfacial structure developed upon irradiation, are beneficial to magnetic loss and interfacial polarization loss, thereby rendering Co 3 O 4 a promising candidate as an effective EMW absorber., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: The Qnox index is a novel monitor to quantify intraoperative nociception based on an electroencephalographic algorithm. We evaluated the ability of the Qnox index to discriminate noxious from non-noxious stimuli, respond to stimuli, and discriminate different levels of analgesia in patients under propofol anaesthesia with neuromuscular block., Methods: Qnox was compared with heart rate and mean arterial pressure with five designated stimuli: tetanic stimulations without (tetanic 1) and with sufentanil (tetanic 2), skin incision, tracheal intubation, and a non-noxious period. The response around the skin incision was also evaluated at two target remifentanil concentrations., Results: In 83 adult patients scheduled for elective surgery, Qnox performed worse than heart rate and mean arterial pressure in discriminating tetanic 2, tetanic 1, skin incision, and tracheal intubation noxious stimuli from the non-noxious period, with an area under curve of 0.52 (95% confidence interval 0.43-0.61), 0.54 (0.45-0.62), 0.67 (0.58-0.75), and 0.65 (0.57-0.73), respectively. The post-stimulus values of Qnox increased significantly after tracheal intubation and skin incision, but not after tetanic 1 or tetanic 2. Qnox values after skin incision were similar between the low- and high-remifentanil-concentration groups., Conclusions: Qnox had a poor ability to discriminate noxious stimuli from non-noxious stimuli. Although Qnox responded to tracheal intubation and skin incision, it did not respond to tetanic stimulations and failed to discriminate different levels of analgesia. The Qnox index was not superior to heart rate or mean arterial pressure in assessing nociception during general anaesthesia., Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100046063)., Competing Interests: Declarations of interest HZ received grants from the Wu Jieping Medical Foundation (number: 320.6750.2020-21-14); HK received grants from the National High-Level Hospital Clinical Research Funding (Interdepartmental Research Project of Peking University First Hospital) (number: 2023IR22), and the Youth Clinical Research Project of Peking University First Hospital (number: 2021CR19)., (Copyright © 2025 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Teletherapy via videoconferencing has become common practice but has unique challenges. We aimed to develop and validate the first performance-based observer-rated measure of teletherapy skills: The Teletherapy Facilitative Interpersonal Skills Performance Task (Tele-FIS). Methods: We developed a set of 12 Tele-FIS video stimulus clips as simulations of four research-informed common therapeutic challenges in teletherapy: technology, distraction, boundaries and privacy, and emotional disconnection. A total of 153 therapists recorded interventions to the clips which were later rated on interpersonal skills. Results: The Tele-FIS performance task demonstrated good interrater reliability, internal consistency, test-retest reliability, and convergent validity. The Tele-FIS was positively associated with self-reported facilitative interpersonal skills, self-efficacy, attitudes towards technology, and observer-rated skills on a version of the FIS task that simulates in-person therapy. Therapists performed similarly on teletherapy clips of emotional disconnection and privacy issues compared to clips of in-person therapy. Therapists performed worse on Tele-FIS clips of technology and distraction challenges than in-person therapy clips. Conclusions: The Tele-FIS has potential as an assessment tool in skills training for trainees and licensed clinicians as well as future research about therapeutic work via teletherapy. Results are discussed to consider therapist skill and the use of practice-relevant materials in training.

Despite major progress in the investigation of boron cluster anions, direct experimental study of neutral boron clusters remains a significant challenge because of the difficulty in size selection. Here we report a size-specific study of the neutral B 9 cluster using threshold photoionization with a tunable vacuum ultraviolet free electron laser. The ionization potential of B 9 is measured to be 8.45±0.02 eV and it is found to have a heptagonal bipyramid D 7h structure, quite different from the planar molecular wheel of the B 9 - anionic cluster. Chemical bonding analyses reveal superior stability of the bipyramidal structure arising from delocalized σ and π bonding interactions within the B 7 ring and between the B 7 ring and the capping atoms. Photoionization of B 9 breaks the single-electron B-B bond of the capping atoms, which undergo off-axis distortion to enhance interactions with the B 7 ring in the singlet ground state of B 9 + . The single-electron B-B bond of the capping atoms appears to be crucial in stabilizing the D 7h structure of B 9 . This work opens avenues for direct size-dependent experimental studies of a large variety of neutral boron clusters to explore the stepwise development of network structures., (© 2025 Wiley-VCH GmbH.)

Prostate cancer (PCa) is mainly managed with androgen deprivation therapy (ADT), but this often leads to a dormant state and subsequent relapse as lethal castration-resistant prostate cancer (CRPC). Using our unique PCa patient-derived xenograft (PDX) dormancy models, we investigated this critical dormant phase and discovered a selective increase in B7-H4 expression during the dormancy period following mouse host castration. This finding is supported by observations in clinical specimens of PCa patients treated with ADT. Differential expression analyses revealed the enrichment of extracellular matrix (ECM)-cell interaction pathways in B7-H4-positive cells. Functional assays demonstrated a crucial role of B7-H4 in maintaining dormancy within the ECM niche. Specifically, B7-H4 expression in LNCaP cells reduced proliferation within dormant ECM in vitro and significantly delayed relapse in castrated hosts in vivo. These results shed light on the dynamic regulation of B7-H4 during PCa dormancy and underscore its potential as a therapeutic target for preventing CRPC relapse. Implications: Our study identified membranous B7-H4 expression during ADT-induced dormancy, highlighting its potential as a therapeutic target for managing dormant prostate cancer and preventing fatal CRPC relapse.

Viral mimicry refers to an active antiviral response triggered by the activation of endogenous retroviruses (ERVs), usually manifested by the formation of double-stranded RNA (dsRNA) and activation of the cellular interferon response, which activates the immune system and produces anti-tumor effects. Epigenetic studies have shown that epigenetic modifications (e.g. DNA methylation, histone modifications, etc.) play a crucial role in tumorigenesis, progression, and treatment resistance. Particularly, alterations in DNA methylation may be closely associated with the suppression of ERVs expression, and treatment by demethylation may restore ERVs activity and thus strengthen the tumor immune response. Therefore, we propose that viral mimicry can induce immune responses in the tumor microenvironment by activating the expression of ERVs, and that epigenetic alterations may play a key regulatory role in this process. In this paper, we review the intersection of viral mimicry, epigenetics and tumor immunotherapy, and explore the possible interactions and synergistic effects among the three, aiming to provide a new theoretical basis and potential strategies for cancer immunotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The genomic landscape of esophageal squamous cell carcinoma (ESCC) has been characterized extensively, but there remains a significant need for actionable targets and effective therapies., Methods: Here, we perform integrative analysis of genome-wide loss of heterozygosity and expression to identify potential tumor suppressor genes. The functions and mechanisms of one of the candidates, TACC2, are then explored both in vitro and in vivo, leading to the proposal of a therapeutic strategy based on the concept of synthetic lethality., Findings: We reveal that the inactivation of TACC2, due to copy number loss and promoter hypermethylation, is associated with poor prognosis in ESCC patients. TACC2 depletion enhances ESCC tumorigenesis and progression, as demonstrated in Tacc2 knockout mouse models and by increased growth abilities of ESCC cells. Mechanistically, TACC2 interacts with components of the NuRD and CoREST co-repressor complexes, including MTA1, MBD3, and HMG20B, in the cytoplasm. TACC2 loss leads to the translocation of these proteins into the nucleus, facilitating the formation of functional NuRD and CoREST complexes and the epigenetic repression of CDKN1A. This repression results in elevated CDK1/2 activation. Furthermore, TACC2-deficient cells and ESCC patient-derived organoids with reduced TACC2 expression show increased sensitivity to CDK inhibitors, particularly dinaciclib, which is currently in a phase III trial. Notably, the combination of TACC2-specific RNAi and dinaciclib in subcutaneous ESCC models significantly impairs tumor growth., Conclusions: The findings suggest a strategy for cancer treatment based on synthetic lethality., Funding: Funded by NKRDP, NSFC, GDIIET, GDBABRF, GDECISTP, and SYSUTP., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Small gastric subepithelial tumors (SETs) in the stomach can be managed through surveillance or resection. However, it is still controversial how often the lesion would progress if left untreated. This study aimed to evaluate the progression rate of small SETs and identify risk factors influencing tumor growth., Methods: PubMed, Cochrane Library, Web of Science, and Scopus were searched for relevant studies until March 2023. Patient information, endoscopic features of SETs, and surveillance information were extracted from each included study. A random-effects model was applied along with subgroup and sensitivity analyses., Results: Based on 14 studies with 5405 SETs smaller than 3.5 cm, the annual incidence of size increase was 4.0 (95%CI 2.2-5.8) per 100 person-years, and the overall incidence was 12.8% (95%CI 8.3%-17.3%) across a surveillance duration of 51.3 ± 16.9 months. The predicted risk factors for tumor growth included ≥ 1 cm lesion size (1-2 cm vs. < 1 cm, OR 2.61, 95%CI 1.80-3.79; and > 2 cm vs. 1-2 cm, OR 1.25, 95%CI 0.87-1.81), origin in the muscularis propria (OR 2.09, 95%CI 1.41-3.10), mucosal change (OR 3.27, 95%CI 1.95-5.50), irregular margin (OR 3.16, 95%CI 1.15-8.69), and hypoechoic pattern (OR 3.06, 95%CI 1.34-7.00)., Conclusions: Most small gastric SETs, particularly those smaller than 1 cm, did not increase in size during surveillance. Special attention should be given to lesions larger than 1 cm, originating from the muscularis propria, or exhibiting mucosal change, irregular margin, and hypoechoic pattern., Competing Interests: Declarations. Disclosures: Xin Dong, Li Gao, Kai Liu, Jiawei Bai, Jiaqiang Dong, Nian Fang, Ying Han, and Zhiguo Liu have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nasopharyngeal carcinoma (NPC) presents a substantial clinical challenge due to the limited understanding of its genetic underpinnings. Here we conduct the largest scale whole-exome sequencing association study of NPC to date, encompassing 6,969 NPC cases and 7,100 controls. We unveil 3 germline genetic variants linked to NPC susceptibility: a common rs2276868 in RPL14, a rare rs5361 in SELE, and a common rs1050462 in HLA-B. We also underscore the critical impact of rare genetic variants on NPC heritability and introduce a refined composite polygenic risk score (rcPRS), which outperforms existing models in predicting NPC risk. Importantly, we reveal that the polygenic risk for NPC is mediated by EBV infection status. Utilizing a comprehensive multiomics approach that integrates both bulk-transcriptomic (n = 356) and single-cell RNA sequencing (n = 56) data with experimental validations, we demonstrate that the RPL14 variant modulates the EBV life cycle and NPC pathogenesis. Furthermore, our data indicate that the SELE variant contributes to modifying endothelial cell function, thereby facilitating NPC progression. Collectively, our study provides crucial insights into the intricate genetic architecture of NPC, spotlighting the vital interplay between genetic variations and tumor microenvironment components, including EBV and endothelial cells, in predisposing to NPC. This study opens new avenues for advancements in personalized risk assessments, early diagnosis, and targeted therapies for NPC.

Quantitative structure-retention relationship (QSRR) is an important tool in chromatography. QSRR examines the correlation between molecular structures and their retention behaviors during chromatographic separation. This approach involves developing models for predicting the retention time (RT) of analytes, thereby accelerating method development and facilitating compound identification. In addition, QSRR can be used to study compound retention mechanisms and support drug screening efforts. This review provides a comprehensive analysis of QSRR workflows and applications, with a special focus on the role of artificial intelligence-an area not thoroughly explored in previous reviews. Moreover, we discuss current limitations in RT prediction and propose promising solutions. Overall, this review offers a fresh perspective on future QSRR research, encouraging the development of innovative strategies that enable the diverse applications of QSRR models in chromatographic analysis., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Ongoing efforts to improve sheep reference genome assemblies still leave many gaps and incomplete regions, resulting in a few common failures and errors in genomic studies. Here, we report a 2.85-Gb gap-free telomere-to-telomere genome of a ram (T2T-sheep1.0), including all autosomes and the X and Y chromosomes. This genome adds 220.05 Mb of previously unresolved regions and 754 new genes to the most updated reference assembly ARS-UI&#95;Ramb&#95;v3.0; it contains four types of repeat units (SatI, SatII, SatIII and CenY) in centromeric regions. T2T-sheep1.0 has a base accuracy of more than 99.999%, corrects several structural errors in previous reference assemblies and improves structural variant detection in repetitive sequences. Alignment of whole-genome short-read sequences of global domestic and wild sheep against T2T-sheep1.0 identifies 2,664,979 new single-nucleotide polymorphisms in previously unresolved regions, which improves the population genetic analyses and detection of selective signals for domestication (for example, ABCC4) and wool fineness (for example, FOXQ1)., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background/purpose: Artificial intelligence (AI) can assist in medical diagnosis owing to its high accuracy and efficiency. This study aimed to develop a diagnostic system for automatically determining the degree of tooth wear (TW) using intraoral photographs with deep learning., Materials and Methods: The study included 388 intraoral photographs. A tooth segmentation model was first established using the Mask R-CNN architecture, which incorporated U-Net and SGE attention mechanisms. Subsequently, 2774 individual tooth images output from the segmentation model were included into the classification task, labeled and randomized into training, validation, and test sets with 6.0:2.0:2.0 ratio. A vision transformer model optimized using a mask mechanism was constructed for TW degree classification. The models were evaluated using the accuracy, precision, recall, and F1-score metrics. The time required for AI analysis was calculated., Results: The accuracy of the tooth segmentation model was 0.95. The average accuracy, precision, recall, and F1-score in the classification task were 0.93, 0.91, 0.88, and 0.89, respectively. The F1-score differed in different grades (0.97 for grade 0, 0.90 for grade 1, 0.88 for grade 2, and 0.82 for grade 3). No significant difference was observed in the accuracy between different surfaces. The AI system reduced the time required to grade an individual tooth surface to 0.07 s, compared to the 2.67 s required by clinicians., Conclusion: The developed system provides superior accuracy and efficiency in determining TW degree using intraoral photographs. It might assist clinicians in the decision-making for TW treatment and help patients perform self-assessments and disease follow-ups., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.Vé.)

Four novel halophilic archaeal strains CGA53 T , CG83 T , FCH27 T , and SEDH24 were isolated from a soda lake and two saline lakes in China, respectively. Strain CGA53 T showed the highest 16S rRNA gene similarity (92.6%) to Salinilacihabitans rarus AD-4 T , and the other three strains were found to be related to Halalkalicoccus species with similarities of 97.6-98.3%. Metagenomic studies indicated that these four strains are low abundant inhabitants detected in these hypersaline environments, and only one MAG of Chagannuoer Soda Lake (CG) could be assigned to the genus Halalkalicoccus. Their growth occurred at 20-60 °C (optima, 42, 37, 37-42, and 35 °C), 0.9-5.1 M NaCl (optima, 3.9, 2.6, 3.5, and 3 M), and 0-1.0 M MgCl 2 (optima, 0.5, 0.7, and 0.1) and pH 5.5-10.5 (optima, 9.0, 7.5, 7.0, and 7.0), respectively. Phylogenetic and phylogenomic analyses revealed that strains CG83 T , FCH27 T , and SEDH24 cluster with the current species of the genus Halalkalicoccus, and strain CGA53 T forms an independent branch separated from this genus. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and average amino acid identity (AAI) values among strains CGA53 T , CG83 T , FCH27 T , SEDH24, and the type species of the current genera within the class Halobacteria were 67.4-81.6%, 16.5-28.6% and 49.7-74.1%, respectively, clearly lower than the cutoff values for species demarcation. Strain CGA53 T may represent a novel species of a new genus according to the cutoff value for genus demarcation of 65% AAI. Diverse differential phenotypic characteristics, such as nutrition, biochemical activities, antibiotic sensitivity, and H 2 S formation, were found among these four strains and Halalkalicoccus species. Genome-based classification supported that strains CGA53 T , CG83 T , FCH27 T , SEDH24, and the current species of Halalkalicoccus represent a novel family of the order Halobacteriales within the class Halobacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome, proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial scRNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field, offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis., Competing Interests: Compliance and ethics. The author(s) declare that they have no conflict of interest., (© 2024. Science China Press.)

Purpose: Optimal local treatment for pulmonary oligometastases from colorectal cancer (CRC) remains unclear. We aimed to compare the long-term survival outcomes between surgery and stereotactic body radiation therapy (SBRT) as the initial local treatment for CRC pulmonary oligometastases., Materials and Methods: We retrospectively reviewed 335 consecutive patients who initially underwent surgery or SBRT for CRC pulmonary metastases from 2011 to 2022, and 251 patients (173 surgery and 78 SBRT) were ultimately included. Freedom from intrathoracic progression (FFIP), progression-free survival (PFS), and overall survival (OS) were compared using stabilized inverse probability of treatment weighting (sIPTW) analysis. In addition, patterns of intrathoracic progression and subsequent treatment were analyzed., Results: Median follow-up was 61.6 months for surgery and 54.4 months for SBRT. After sIPTW adjustment, significant differences emerged in both FFIP and PFS between surgery and SBRT (FFIP: hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.31-0.79; PFS: HR = 0.56, 95% CI, 0.36-0.87). The 3- and 5-year FFIP rates were 58.6% and 54.8%, respectively, after surgery, and 34.6% and 31.3%, respectively, after SBRT (P = .006). The 3- and 5-year PFS rates were 49.4% and 45.2%, respectively, after surgery, and 28.8% and 26.1%, respectively, after SBRT (P = .010). However, OS was not significantly affected by treatment approach (HR = 0.93, 95% CI, 0.49-1.76). The 3- and 5-year OS rates were 85.9% and 73.1%, respectively, after surgery, and 78.9% and 68.7%, respectively, after SBRT (P = .849). Recurrence at the treated site was more prevalent after SBRT than after surgery (33.3% vs 16.9%), whereas new intrathoracic tumors occurred more frequently after surgery than after SBRT (71.8% vs 43.1%). Both groups chose radiation therapy as the primary local salvage treatment., Conclusions: Notwithstanding the significant differences in FFIP and PFS between surgery and SBRT, the long-term survival of patients with CRC pulmonary oligometastases did not depend on the initial choice of the local treatment approach., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Statement of Problem: The selective laser melting (SLM) technique has been a promising method of fabricating Co-Cr metal-ceramic restorations; however, the lower metal-ceramic bond properties of SLM Co-Cr restorations have become a major issue in clinical use., Purpose: The purpose of this in vitro study was to propose and verify a method of improving the metal-ceramic bond properties of SLM Co-Cr alloy with heat treatment after porcelain firing (PH)., Material and Methods: Forty-eight (25×3×0.5 mm) Co-Cr specimens, divided into 6 groups (Control group [CG]; 550 °C; 650 °C; 750 °C; 850 °C; 950 °C) according to PH temperatures, were prepared by using SLM techniques. The 3-point bend tests were performed to evaluate the metal-ceramic bond strengths; subsequently, the fracture feature was assessed by using a digital camera and scanning electron microscope (SEM) coupled with an energy-dispersive X-ray spectroscopy (EDS) detector, to determine the area fraction of adherence porcelain (AFAP). The interface morphologies and element distribution were determined with SEM/EDS detectors. Phase identification and quantification were examined with an X-ray diffractometer (XRD). A 1-way ANOVA and the Tukey honestly significant difference tests were used to analyze bond strengths and AFAP values (α=.05)., Results: The bond strengths were 35.33 ±1.25 MPa for the CG group, 34.53 ±3.20 MPa for the 550 °C group, 38.20 ±2.60 MPa for the 650 °C group, 42.85 ±2.31 MPa for the 750 °C group, 33.28 ±3.85 MPa for the 850 °C group, and 29.09 ±2.86 MPa for the 950 °C group. Significant differences were not observed among the CG, 550 °C, and 850 °C groups (P>.05) but were found among the other groups (P<.05). Fracture and AFAP results displayed a mixed fracture mode of adhesive and cohesive fracture. The thicknesses of native oxide films across the 6 groups were relatively close as the temperature increased, but the thickness of the diffusion layer increased as well. Excessive oxidation and massive phase transformation caused holes and microcracks to appear in the 850 °C and 950 °C groups, reducing bond strengths. XRD analysis evidenced that the phase transformation of γ→ε occurred at the interface during PH treating., Conclusions: PH treatment significantly affected the metal-ceramic bond properties of SLM Co-Cr porcelain specimens. The 750 °C-PH-treated specimens displayed higher mean bond strengths and improved fracture characteristics among the 6 groups., (Copyright © 2023 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Persistent myocardial impairment proved by histopathologic studies universally existed in patients with Kawasaki disease (KD); however, the long-term effects on myocardial contractile reserve in KD patients, especially on patients without coronary artery lesions (CALs), is still unknown. The aim of this study was to investigate myocardial contractile reserve in KD patients during late convalescent stage by speckle-tracking adenosine triphosphate (AT) echocardiography. A total of 63 antecedent KD patients at least 4 years after the disease onset and 40 age- and gender-matched normal controls were prospectively enrolled. Based on coronary artery status, patients were further divided into CALs group and non-CALs (NCALs) group. Left ventricular ejection fraction (LVEF), speckle-tracking derived-global longitudinal strain (GLS), and global circumferential strain (GCS) were evaluated at rest and during AT peak stress. Myocardial contractile reserve parameters including ΔLVEF, ΔGLS, and ΔGCS were defined as the absolute value differences in LVEF, GLS, and GCS from rest to peak stress. Of the patients with KD, 44 had normal coronary artery and 19 had CALs. KD patients regardless of CALs had lower GLS and GCS than normal controls at resting condition. Significant decreases in ΔGLS and ΔGCS were observed in patients with CALs compared to normal controls under peak stress. While ΔGLS and ΔGCS increased in patients without CALs following stress, improvements were significantly weaker than those in normal controls. However, no significant differences in LVEF at rest and ΔLVEF under peak stress between KD patients irrespective of CALs and normal controls were found. In addition, when comparing with patients with NCALs, patients with CALs had lower GLS and GCS at rest and lower ΔGLS and ΔGCS in response to stress. Subclinical abnormality of myocardial contractile reserve existed in KD patients during late convalescent phase. Even patients without CALs need an additional surveillance on myocardial contractile reserve in the long-term follow-up. These novel findings by speckle-tracking stress echocardiographic analysis may provide more valuable clinical implications for better understanding and long-term management of such patients., Competing Interests: Declarations. Conflict of interest: There are no authors’ financial ties to products in the study or potential/perceived conflicts of interest on the cover page., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown., Purpose: This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms., Methods: A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/β-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC., Results: CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/β-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/β-catenin pathway., Conclusions: This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the impact of dexmedetomidine-ropivacaine combination versus sufentanil-ropivacaine combination for epidural labour analgesia on neonatal and maternal outcomes and test the feasibility of a future large, randomised trial., Design: A randomised, double-blind, pilot clinical trial from 16 March 2023 to 15 June 2023., Setting: A tertiary-care hospital in Beijing, China., Participants: 200 women aged≥18 years who had full-term single pregnancy and were scheduled for vaginal delivery with epidural analgesia., Interventions: Eligible participants were randomly assigned in a 1:1 ratio to receive self-controlled epidural labour analgesia using ropivacaine supplemented with either dexmedetomidine (0.45 µg/mL for induction and 0.36 µg/mL for maintenance) or sufentanil (0.45 µg/mL for induction and 0.36 µg/mL for maintenance)., Main Outcomes and Measures: The primary endpoint was a composite of neonatal morbidity, including 1- or 5 min Apgar score<7, umbilical artery PH<7.1, requirement for immediate assisted ventilation and admission to neonatal ward or intensive care unit within 24 hours. Secondary and other endpoints included effect of analgesia and occurrence of adverse events. The feasibility of implementing the protocol was evaluated., Results: All 200 women were included in the intention-to-treat analysis. Composite neonatal morbidity occurred in 14.0% (14/100) of women with dexmedetomidine versus 17.0% (17/100) of women with sufentanil: relative risk 0.82, 95% CI 0.43 to 1.58. Women in the dexmedetomidine group had a comparable area under curve of pain intensity (median difference -2.0 point⋅h, 95% CI -9.9 to 5.9, p=0.638), required more self-controlled boluses (median difference two boluses, 95% CI 0 to 3, p=0.040) and epidural analgesics (median difference 17 mL, 95% CI 4 to 29, p=0.007), and experienced less pruritus (0.0% (0/100) vs 30.0% (30/100), p<0.001) but more lower limb weakness (13.0% (13/100) vs 1.0% (1/100), p<0.001). Recruitment rate was satisfactory (87.7%); the protocol was well accepted by anaesthesiologists and nurses., Conclusions: Compared with sufentanil-ropivacaine combination, use of dexmedetomidine-ropivacaine combination for epidural labour analgesia was associated with a 18% decrease in composite neonatal endpoint and deserve further investigation. The dexmedetomidine-ropivacaine combination provided comparable analgesia but increased mild motor block. The conduct of a large, randomised trial using same protocol requires careful re-evaluation., Trial Registration Number: NCT05698407., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

It is urgently desired to develop high-performance wind energy collectors to power numerous microelectronic devices along with the Internet of Things (IoT). A roller-type triboelectric nanogenerator (R-TENG) based on rotational friction between wool and stacked interfaces is proposed and efficiently used for harvesting wind energy. Wool, an electropositive and flexible material, is utilized in the design, effectively reducing abrasion on the contact surface and adjusting the output in response to varying compression levels. The conductive layer greatly enhances the output performance, which produces more induced charge by stacking different triboelectric materials in a particular order. By adding bottom power generation units, the internal space of the unit can be fully utilized to improve its energy conversion efficiency. At 900 rpm of the motor, the instantaneous open-circuit voltage ( V OC ), short-circuit current ( I SC ), and transferred charge ( Q SC ) of the R-TENG can reach 1504 V, 67.24 μA and 157.4 nC, respectively. After connection to a load via a rectifier bridge, the R-TENG has a maximum power output of 14.58 mW and an instantaneous power density of 11.7 W m -3 . In laboratory wind energy harvesting experiments, the design can easily drive at least 720 LEDs and charge a 2000 μF capacitor up to about 1.5 V in 78 s. In practice, the R-TENG can collect natural wind on windy seashores and moving vehicles to charge capacitors and successfully drive small electronic devices in real time. The experimental results indicate that the stacked PTFE/FKM/Wool R-TENG exhibits considerable output performance, making it a promising solution for efficiently capturing wind energy from all directions.

Background: Overtime work is common in anesthesiologists due to shortage of manpower. Herein, we analyzed if overtime work of anesthesiologists was associated with delirium development in older patients after surgery., Methods: This was a secondary analysis of the database from a randomized trial. Seven hundred older patients (aged ≥ 65 years) who were admitted to the intensive care unit (ICU) after elective noncardiac surgery were enrolled in the underlying trial. Anesthesiologists who worked continuously for more than 8 h by the end of the surgery were marked as "work overtime". Delirium was assessed with the Confusion Assessment Method for the ICU twice daily during the first 7 postoperative days. The association between overtime work of anesthesiologists and development of postoperative delirium was analyzed with multivariable logistic regression models., Results: All 700 patients (mean age 74.3 years, 39.6% female) were included in this analysis. Anesthesiologists of 281 patients (40.1%) were marked as "work overtime" at the end of surgery. When compared with patients whose anesthesiologists didn't work overtime, patients whose anesthesiologist worked overtime had a higher incidence of delirium within 7 days (20.3% [57/281] vs. 12.9% [54/419], P = 0.009). After correction for confounding factors, both overtime work (OR 1.87, 95% CI 1.19-2.94, P = 0.007) and prolonged continuous working hours of anesthesiologists (OR 1.08, 95% CI 1.01-1.15, P = 0.020) were associated with an increased risk of postoperative delirium., Conclusions: Overtime work of anesthesiologists was associated with an increased risk of delirium development in older patients admitted to ICU after major noncardiac surgery., Trial Registration: The underlying trial was registered with Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=8734 ; ChiCTR-TRC-10000802; March 18, 2010)., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Biomedical Research Ethics Committee of Peking University First Hospital on October 27, 2022 (2022[470]). Ethical approval for the original study was provided by the Clinical Research Ethics Committee of Peking University First Hospital (Chairperson Prof Guo Xiaohui) and registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-10000802). Participants or their legal representatives were provided informed consent prior to enrollment into the original study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Poor oral health, prevalent among the older adults, can undermine overall health and contribute to frailty. Older adults experiencing oral frailty and dysbiosis potentially face an elevated risk of postoperative delirium. This study aims to explore the influence of oral frailty and changes in oral microbiota composition on occurrence of postoperative delirium in older adult patients undergoing non-cardiac surgery., Methods: A total of 303 older adult patients undergoing non-cardiac surgeries were recruited in the Second Affiliated Hospital of Nanjing Medical University from July 2023 to December 2023. Oral swabs for oral microbiota analyses were collected before surgery. Subsequently, after propensity score matching, 21 samples from patients with postoperative delirium and 21 samples from patients without postoperative delirium were analyzed for oral microbiota. Our primary objective was to determine the association between oral frailty, changes in oral microbiota composition, and the occurrence of postoperative delirium., Results: Oral frailty emerged as an independent risk factor for postoperative delirium [HR = 1.75; 95% CI = (1.04-2.96); p = 0.035]. Additionally, patients with postoperative delirium demonstrated lower oral microbiota diversity, as indicated by a reduced Chao index compared with those without postoperative delirium (p = 0.034). A significant association was also found between the dysbiosis index and postoperative delirium (p < 0.001). ROC analysis revealed a pronounced area under the curve of 0.95 (95% CI: 0.88-1.00) for the dysbiosis index in predicting postoperative delirium. Subsequent Principal Coordinates and Kaplan-Meier analyses affirmed that both beta diversity and the dysbiosis index were significantly correlated with incidence of postoperative delirium, with p-values of 0.002 and <0.001, respectively. Furthermore, the interaction analysis through Cox proportional hazards regression suggested a combined effect of oral frailty and the dysbiosis index on the likelihood of developing postoperative delirium (p = 0.004)., Conclusions: Oral frailty and changes in oral microbiota among older adult patients undergoing non-cardiac surgery may influence the incidence of postoperative delirium., (© 2024 The American Geriatrics Society.)

Dyslipidemia is responsible for pathologies of cardiovascular diseases and gut microbiota plays an essential role in lipid metabolism. Dietary supplementation is an important supplement to medicine in management of dyslipidemia. Mori Fructus is a popular Asia medical food with various pharmacological benefits including anti-hyperlipidemia. Cyanidin-3-rutinoside (C3R) is the main anthocyanin component in Mori Fructus, but the lipid-lowering effect and underlying mechanism of Mori Fructus-derived C3R remains unknown. In this study, we assessed the beneficial effect of Mori Fructus-derived C3R in HFD-induced hyperlipidemic mice and investigated its potential mechanism through 16S rRNA-based metagenomics and transcriptomics analysis. Our results showed that C3R from Mori Fructus significantly decreased serum lipid levels and attenuated hepatic damage induced by HFD. Analysis of the gut microbiota revealed that C3R altered the specific gut micorbiota but not changed its diversity. Among changed genera, Family&#95;XIII&#95;UCG-001 was significantly enriched by C3R, and it was positively associated with HDL-c, but negatively related with TC, TG, LDL-c, insulin and body weight. Transcriptomic analysis showed that C3R activates the lipid metabolism related pathways including MAPK signaling pathway, Rap1 signaling pathway, Ras signaling pathway and PI3K-Akt signaling pathway. Additionally, correlation analysis unraveled that C3R-enriched Family&#95;XIII&#95;UCG-001 was negatively associated with C3R-inhibited genes of Camk2a, Eef1a2, Gad1, Kif5a and Sv2b, which further positively related with TC, TG, LDL-c, insulin and body weight, but negatively associated with HDL-c. In sum, C3R may inhibit expression of immune-related genes by enriching the Family&#95;XIII&#95;UCG-001 genus, further ameliorating lipid metabolism disorders in HFD-challenged mice. This study provides an optional strategy for the daily management of dyslipidemia., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Glycogen is a glucose polymer that plays a crucial role in glucose homeostasis by functioning as a short-term energy storage reservoir in animals and bacteria. Abnormalities in its metabolism and structure can cause several problems, including diabetes, glycogen storage diseases (GSDs) and muscular disorders. Defects in the enzymes involved in glycogen synthesis or breakdown, resulting in either excessive accumulation or insufficient availability of glycogen in cells seem to account for the most common pathogenesis. This review discusses glycogen metabolism and structure, including molecular architecture, branching dynamics, and the role of associated components within the granules. The review also discusses GSD type XV and Lafora disease, illustrating the broader implications of aberrant glycogen metabolism and structure. These conditions also impart information on important regulatory mechanisms of glycogen, which hint at potential therapeutic targets. Knowledge gaps and potential future research directions are identified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Caryopteris mongolica Bunge (CM) shows promising potential for managing rheumatoid arthritis (RA) and digestive disorders, attributed to its rich content of bioactive compounds such as polyphenols and flavonoids. Despite its common use in herbal tea, the specific mechanisms underlying CM's anti-inflammatory and joint-protective effects remain unclear, limiting its development as a functional food. This study investigated the effects of aqueous CM extract on RA in collagen-induced arthritis (CIA) rats and explored the underlying mechanisms., Methods: Forty-eight female Sprague-Dawley rats were randomly assigned to six groups ( n = 8): normal control, CIA model, methotrexate (MTX), and CM high-, middle-, and low-dose groups. Anti-inflammatory and joint-protective effects were evaluated using biochemical and histological analyses. To elucidate the mechanisms, we applied metabolomics, network pharmacology, and transcriptomics approaches., Results: The results demonstrated that CM extract effectively suppressed synovial inflammation in CIA rats, reducing joint degradation. CM's anti-inflammatory effects were mediated through the TNF signaling pathway, modulating glycerophospholipid and amino acid metabolism, including reduced levels of tryptophan, LysoPC, and asparagine. Molecular docking identified scutellarin and apigenin as key bioactive compounds. Additionally, immunofluorescence analysis revealed CM's therapeutic effects via TNF signaling inhibition and suppression of M1 macrophage polarization., Conclusions: These findings highlight the therapeutic potential of CM for RA and support its development as a functional food or pharmaceutical product.

Environmental factors lead mainly to the uncertainty of gross primary productivity estimation in most light use efficiency (LUE, ε) models since the simple physical formulas are inadequate to fully express the overall constraint of diverse environmental factors on the maximum ε (ε max ). In contrast, machine learning has the natural potential to detect intricate patterns and relationships among various environmental variables. Here, we presented a hybrid model (TL-CRF) that utilizes the random forest (RF) technique to incorporate various ecological stress factors into the two-leaf LUE (TL-LUE) model, meanwhile, seasonal differences in the clumping index (CI) on a global scale are considered to adjust seasonal patterns of canopy structure. The comprehensive integration of complex environmental variables based on this RF submodule is conducive to scaling theoretical ε max to actual ε as much as possible. The proposed TL-CRF model considerably improves global GPP estimation by complementing innate advantages between the process-based and data-driven models.•The seasonal CI averages in different stages of the leaf life cycle are estimated for different vegetation types on a global scale.•Various environmental stress factors are integrated via the RF technique.•The RF submodule is embedded into the TL-LUE model to establish a hybrid model., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

M2 macrophage-derived extracellular vesicles (M2-EVs) demonstrate the capacity to reduce pro-inflammatory M1 macrophage formation, thereby restoring the M1-M2 macrophage balance and promoting immunoregulation. However, the efficacy of M2-EVs in regulating macrophage polarization and subsequently enhancing osseointegration around titanium (Ti) implants in patients with diabetes mellitus (DM) remains to be elucidated. In this study, Ti implants were coated with polydopamine to facilitate M2-EVs adherence. In vitro experiment results demonstrated that M2-EVs could carry miR-23a-3p, inhibiting NOD-like receptor protein3(NLRP3) inflammasome activation in M1 macrophage and reducing the levels of inflammatory cytokines such as IL-1β by targeting NEK7. This improved the M1-M2 macrophage balance and enhanced mineralization on the Ti implant surfaces. The in vivo experiment results demonstrated that in diabetic conditions, the nanocoated M2-EVs significantly promoted high-quality bone deposition around the Ti implants. The current results provide a novel perspective for simple and effective decoration of M2-EVs on Ti implants; clinically, the method may afford osteoimmunomodulatory effects enhancing implant osseointegration in patients with DM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Dexmedetomidine may improve sleep quality after surgery, but conflicting results also exist. Herein, we explored the effects of perioperative dexmedetomidine on postoperative sleep quality in adult patients., Methods: In this systematic review and meta-analysis, randomized controlled trials investigating the effects of perioperative dexmedetomidine on sleep quality after noncardiac surgery were retrieved from Cochrane Library, PubMed, and EMBASE from inception to January 12, 2023, and updated on March 15, 2024. The Cochrane Collaboration's tool was applied to assess risk of bias. A random-effects model was used for meta-analysis. The primary outcome was the subjective sleep quality score on the first night after surgery., Results: A total of 29 trials containing 5610 participants were included. The subjective sleep score on the first postoperative night was lower (better) with dexmedetomidine than with placebo (SMD [standardized mean difference] = -0.8, 95% CI -1.1 to -0.6, p<0.00001; I2 = 93%; 22 trials; n = 4611). Sensitivity analysis showed that overall conclusion was not changed (SMD = -0.8, 95% CI -1.1 to -0.5, p<0.00001; I2 = 93%; 14 trials; n = 3846). Results of polysomnographic monitoring showed improved sleep structure with dexmedetomidine on the first night after surgery, as manifested by increased sleep efficiency index and stage N2 sleep and decreased arousal index and stage N1 sleep., Conclusions: This systematic review suggests that, among patients who underwent noncardiac surgery, perioperative dexmedetomidine administration may improve early postoperative sleep quality pattern. However, the resulting evidence were of low or very low qualities and further studies are required to confirm our results., Prospero Registration Number: CRD42023390972., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate the associations of the gut microbiota with reproductive system diseases, including female infertility, male infertility, polycystic ovary syndrome (PCOS), primary ovarian failure, endometriosis, uterine fibroids, uterine polyps, sexual dysfunction, orchitis, and epididymitis., Methods: A two-sample bidirectional Mendelian randomization (MR) analysis was performed to evaluate the potential causal relationship between the composition of gut microbiota and infertility, along with associated diseases., Results: Sixteen strong causal associations between gut microbes and reproductive system diseases were identified. Sixty-one causal associations between gut microbes and reproductive system diseases were determined. The genus Eubacterium hallii was a protective factor against premature ovarian failure and a pathogenic factor of endometriosis. The genus Erysipelatoclostridium was the pathogenic factor of many diseases, such as PCOS, endometriosis, epididymitis, and orchitis. The genus Intestinibacter is a pathogenic factor of male infertility and sexual dysfunction. The family Clostridiaceae 1 was a protective factor against uterine polyps and a pathogenic factor of orchitis and epididymitis. The results of reverse causal association analysis revealed that endometriosis, orchitis, and epididymitis all led to a decrease in the abundance of bifidobacteria and that female infertility-related diseases had a greater impact on gut microbes than male infertility-related diseases did., Conclusions: The findings from the MR analysis indicate that there is a bidirectional causal relationship between the gut microbiota and infertility as well as associated ailments. Compared with ovarian diseases, uterine diseases are more likely to lead to changes in women's gut microbiota. The findings of this research offer valuable perspectives on the mechanism and clinical investigation of reproductive system diseases caused by microorganisms., Competing Interests: Conflict of Interest Statement. The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work., (© 2024. Huazhong University of Science and Technology.)

Objective: To investigate the clinical efficacy and safety of Loratadine combined with Glucocorticoid nasal spray in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis., Methods: A total of 100 pediatric patients with moderate to severe bronchial asthma and seasonal allergic rhinitis admitted to our hospital between January 2020 and January 2023 were included in this study. All patients met the complete inclusion and exclusion criteria. Based on different treatment interventions, they were divided into the control group ( n  = 50) and the observation group ( n  = 50). Patients in the control group received treatment with glucocorticoid nasal spray, while patients in the observation group received combined intervention with Loratadine in addition to the treatment received by the control group. The clinical treatment outcomes, incidence of adverse reactions, as well as the scores of nasal symptoms, asthma control, and peak expiratory flow rates at different treatment time points (baseline, T1: 30 days after treatment, T2: 60 days after treatment, T3: 90 days after treatment) were compared between the two groups. The combined treatment of Loratadine with Glucocorticoid nasal spray demonstrates significant clinical efficacy in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. It further promotes the recovery of peak expiratory flow rates, improves symptoms of rhinitis and asthma in pediatric patients. Importantly, the application of this combined treatment does not increase the risk of adverse reactions in pediatric patients, indicating its high safety profile. This treatment approach is worthy of clinical application and further promotion.

Background: Herbal prescription recommendation (HPR) is a hotspot in the research of clinical intelligent decision support. Recently plentiful HPR models based on deep neural networks have been proposed. Owing to insufficient data, e.g., lack of knowledge of molecular, TCM theory, and herbal dosage in HPR modeling, the existing models suffer from challenges, e.g., plain prediction precision, and are far from real-world clinics., Purpose: To address these problems, we proposed a novel herbal prescription recommendation model with the representation fusion of large TCM semantics and molecular knowledge (termed PresRecRF)., Study Design and Methods: PresRecRF comprises three key modules. The representation learning module consists of two key components: a molecular knowledge representation component, integrating molecular knowledge into the herb-symptom-protein knowledge graph to enhance representations for herbs and symptoms; and a TCM knowledge representation component, leveraging BERT and ChatGPT to acquire TCM knowledge-enriched semantic representations. We introduced a representation fusion module to effectively merge molecular and TCM semantic representations. In the herb recommendation module, a multi-task objective loss is implemented to predict both herbs and dosages simultaneously., Results: The experimental results on two clinical datasets show that PresRecRF can achieve the optimal performance. Further analysis of ablation, hyper-parameters, and case studies indicate the effectiveness and reliability of the proposed model, suggesting that it can help precision medicine and treatment recommendations., Conclusion: The entire process of the proposed PresRecRF model closely mirrors the actual diagnosis and treatment procedures carried out by doctors, which are better applied in real clinical scenarios. The source codes of PresRecRF is available at https://github.com/2020MEAI/PresRecRF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Study Objective: To test the hypothesis that emergence delirium might be associated with worse long-term survival., Design: A longitudinal prospective observational study., Setting: A tertiary hospital in Beijing, China., Patients: A total of 942 patients aged 65-90 years who were admitted to post-anesthesia care unit (PACU) after major noncardiac surgery under general anesthesia., Exposures: Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay., Measurements: Patients were followed up once a year for at least 3 years. Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. Associations between emergence delirium and long-term survivals were analyzed with the Cox proportional hazard models., Main Results: Among enrolled patients, 915 completed perioperative assessments; 906 completed long-term follow-up (mean age 72 years; 60 % [545/906] male; 73 % [660/906] cancer surgery). At the end of follow-up (median 43 months), there were 69 deaths in 331 patients (21 %) with emergence delirium versus 114 deaths in 575 patients (20 %) without: unadjusted hazard ratio 1.10 (95 % CI: 0.81 to 1.48); P = 0.547; adjusted hazard ratio 0.96 (95 % CI: 0.70 to 1.32); P = 0.797. Recurrence-free survival was 73/331 (22 %) in patients with emergence delirium versus 121/575 (21 %) without: unadjusted hazard ratio 1.08 (95 % CI: 0.81 to 1.45); P = 0.598; adjusted hazard ratio 0.94 (95 % CI: 0.69 to 1.28); P = 0.695. Event-free survival was 159/331 (48 %) in patients with emergence delirium versus 268/575 (47 %) without: unadjusted hazard ratio 1.06 (95 % CI: 0.87 to 1.29); P = 0.563; adjusted hazard ratio 0.98 (95 % CI: 0.80 to 1.21); P = 0.875., Conclusions: We did not find significant association between emergence delirium and worse long-term survival in older patients after general anesthesia and major surgery mainly for cancer. The effects of emergence delirium on long-term outcomes deserve further investigation., Clinical Trial Registrations: www.chictr.org.cn; ChiCTR-OOC-17012734., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: We aimed to provide a comprehensive understanding of the associations between iron metabolism and gestational diabetes mellitus (GDM) by examining multiple iron-related indicators., Methods: We conducted a prospective study involving 907 Chinese pregnant women. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of iron-related indicators during the first trimester (≤ 14 weeks of gestation). GDM outcomes were measured through oral glucose tolerance tests (OGTT) conducted between weeks 24 and 28 of gestation., Results: Subjects with iron-related indicators below the 10th percentile (except for serum iron and soluble transferrin receptor) had a higher risk of GDM compared to normal subjects (10th-90th percentiles). The ORs (95 %CI; p-value) were 1.88 (1.10, 3.20; P=0.020) for ferritin, 1.88 (1.10, 3.19; P=0.020) for hepcidin. Higher levels of ferritin (> 90th percentile) were associated with a higher risk of abnormal fasting blood glucose, while lower levels (< 10th percentile) of ferritin, hepcidin, and transferrin were associated with a higher risk of one-hour postprandial glucose ≥ 8.6 mmol/L in the OGTT., Conclusions: Lower levels (< 10th percentiles) of several iron-related indicators (ferritin, hepcidin, and transferrin) were associated with a higher risk of GDM and abnormal blood glucose compared to normal subjects., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ce prop ) required to suppress response to cervical dilation in patients undergoing hysteroscopy., Methods: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg -1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 μg⋅kg -1 , and a target-controlled propofol infusion. The initial target Ce prop was 3.5 μg·mL -1 and was increased or decreased in subsequent patients by steps of 0.5 μg·mL -1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ce prop that suppressed response to cervical dilation in 50% of patients (EC 50 )., Results: The EC 50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg -1 (2.08 [95% confidence interval, CI, 1.88-2.28] μg·mL -1 ), 0.15 mg⋅kg -1 (1.83 [1.56-2.10] μg·mL -1 ), and 0.2 mg⋅kg -1 (1.43 [1.27-1.58] μg·mL -1 ) remimazolam than those given 0 mg⋅kg -1 (3.67 [3.49-3.86] μg·mL -1 ) or 0.05 mg⋅kg -1 (3.47 [3.28-3.67] μg·mL -1 ) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg -1 decreased EC 50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg -1 ). Propofol consumption was lower in patients given 0.1 mg⋅kg -1 (4.15 [3.51-5.44] mg·kg -1 ), 0.15 mg⋅kg -1 (3.54 [3.16-4.46] mg·kg -1 ), and 0.2 mg⋅kg -1 (2.74 [1.73-4.01] mg·kg -1 ) remimazolam than those given 0 mg⋅kg -1 (6.09 [4.99-7.35] mg·kg -1 ) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups., Conclusions: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg -1 reduced the EC 50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Acute kidney injury (AKI) is common after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal surface malignancies. Herein we analyzed the association between intraoperative hyperthermia and AKI following CRS-HIPEC., Methods: In this retrospective cohort study, we collected baseline and perioperative data from patients who underwent CRS-HIPEC mainly for pseudomyxoma peritonei between 2014 and 2020. Nasopharyngeal temperature was recorded at 5-min intervals. The area above the threshold was calculated for intraoperative hyperthermia (>37.0 °C). AKI was diagnosed and classified according to the KDIGO creatinine criteria. A multivariable logistic regression model was established to assess the association between hyperthermia and AKI., Results: A total of 480 patients were included in the analysis. Of these, 10.6% (51/480) developed AKI within 7 postoperative days. After correction for confounding factors, a larger area above the threshold of hyperthermia was significantly associated with an increased risk of AKI (odds ratio [OR] 1.36, 95% CI 1.14-1.63, p  = 0.001). Among other factors, older age (OR 1.05, 95% CI 1.02-1.09, p  = 0.002), postoperative hypotension requiring vasopressors (OR 2.09, 95% CI 1.02-4.27, p  = 0.042), and intraperitoneal chemotherapy containing cisplatin (OR 2.75, 95% CI 1.20-6.33, p  = 0.017) were also associated with an increased risk of AKI. Patients with AKI required longer mechanical ventilation, stayed longer in the intensive care unit and hospital, developed more complications, and required more intensive care unit readmission., Conclusions: Among patients undergoing CRS-HIPEC, intraoperative hyperthermia was independently associated with a higher risk of AKI; this effect was additive to other risk factors including cisplatin-containing chemotherapy.

Green-gray infrastructure is promising to control urban runoff and pollution, thereby mitigating the impacts of urbanization and climate change on urban water systems. In this study, we developed a novel spatiotemporal optimization framework for planning the construction of green-gray facilities. Construction timing was incorporated as an optimization variable within the framework. An integrated water quality model was established to capture water quality response, which served as the primary decision-making criterion instead of conventional focus on runoff volume or pollutant load reduction. A machine-learning-based emulator, developed based on numerical models, acted as the lake module within the integrated water quality model, thereby ensuring an acceptable runtime for the optimization framework. Compared to traditional ones, our framework could achieve synchronized optimization of the construction timing, location, type, and size of the facilities, ensuring cost-efficiency throughout the planning horizon. This methodology was applied in the Caohai catchment, China, providing Pareto-optimal construction plans of green-gray facilities. Our results reveal the diverse suitability and synergistic interactions within facilities in mitigating water pollution across the area. Broad construction across facility types proved more effective than focusing on a few. Optimal construction timing patterns varied across facilities, shaped by unique cost dynamics and the pressures exerted on each facility by rising levels of urbanization. This underscores the significance of incorporating strategic timing into the planning of green-gray infrastructure. Overall, our novel optimization framework provides an integrated ecological and engineering approach for cost-effective urban green-gray infrastructure planning, thereby advancing sustainable urban growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Motivation: Drug repositioning (DR), identifying novel indications for approved drugs, is a cost-effective strategy in drug discovery. Despite numerous proposed DR models, integrating network-based features, differential gene expression, and chemical structures for high-performance DR remains challenging., Results: We propose a comprehensive deep pretraining and fine-tuning framework for DR, termed DrugRepPT. Initially, we design a graph pretraining module employing model-augmented contrastive learning on a vast drug-disease heterogeneous graph to capture nuanced interactions and expression perturbations after intervention. Subsequently, we introduce a fine-tuning module leveraging a graph residual-like convolution network to elucidate intricate interactions between diseases and drugs. Moreover, a Bayesian multiloss approach is introduced to balance the existence and effectiveness of drug treatment effectively. Extensive experiments showcase the efficacy of our framework, with DrugRepPT exhibiting remarkable performance improvements compared to SOTA (state of the arts) baseline methods (improvement 106.13% on Hit@1 and 54.45% on mean reciprocal rank). The reliability of predicted results is further validated through two case studies, i.e. gastritis and fatty liver, via literature validation, network medicine analysis, and docking screening., Availability and Implementation: The code and results are available at https://github.com/2020MEAI/DrugRepPT., (© The Author(s) 2024. Published by Oxford University Press.)

A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP)., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Serum testosterone (T) in males has been declining during the past decades. The previous reports found that 1-nitropyrene (1-NP) exposure suppressed testicular T synthesis. The purpose of the current study was to further explore whether premature senescence participates in 1-NP-triggered reduction of testicular T synthesis. Adult male mice were orally exposed to 1-NP (0, 100, and 500 μg/kg) daily for 14 days. Serum and testicular T contents were diminished in 1-NP-administered mice. Mitochondria-located steroidogenic synthases, including StAR, CYP11A1, and 3βHSD1, were downregulated in 1-NP-administered mouse testes and MLTC-1 cells. Mechanistically, 1-NP exposure increased acetylation modification of mitochondrial steroidogenic synthases by inhibiting the enzymatic activity of SIRT3, an NAD + -dependent deacetylase. Supplementing NAD  +  precursor and Sirt3 overexpression relieved 1-NP-triggered reduction of steroidogenic synthase levels in mouse testes and MLTC-1 cells. By contrast, Sirt3 silencing aggravated 1-NP-evoked acetylation and reduction of steroidogenic synthase levels in MLTC-1 cells. Further experiments demonstrated that 1-NP exposure caused mitochondrial malfunction and premature senescence in mouse testes and MLTC-1 cells. Supplementation with mitochondria-directed antioxidant mitoquinone (MitoQ) prevented 1-NP-evoked Leydig cell premature senescence and downregulation of testicular steroidogenic synthases. These results suggest that mitochondrial malfunction-initiated Leydig cell premature senescence may partially participate in 1-NP-evoked reduction of steroidogenic synthase levels in testes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Liver fibrosis (LF) is a common sequela to diverse chronic liver injuries, leading to rising rates of cirrhosis and hepatocellular carcinoma (HCC). As the medicinal and edible homologous material, traditional teas have exhibited promising applications in the clinical management of liver fibrosis. Here, we generated a liver fibrosis mouse model to explore the potent therapeutic ability of Ampelopsis grossedentata (AG) tea on this condition by multi-omics analysis. The biochemistry results pointed towards mitigated increases of ALT, AST, TBIL, and ALP triggered by BDL in the AG-treated group. Examination using H&E and Sirius Red staining revealed severe liver injuries, inflammation infiltration, amplified fibrosed regions, and the creation of bile ducts, all of which were fallout from BDL. Immunohistochemistry findings also implicated a noteworthy upregulation of the HSC activation marker α-smooth muscle actin (α-SMA) and the fibrosis marker collagen I in the BDL group. However, these symptoms demonstrated a significant improvement in the group treated with 100 mg/kg AG. Findings from the Western Blot test corroborated the prominent elevation of TNF-α, col1a1, α-SMA, and TGF-β, instigated by BDL, while AG treatment meaningfully modulated these proteins. Furthermore, our study underscored the potential involvement of several microbiota, such as Ruminococcaceae UCG-014, Eubacterium Ruminantium, Ruminococcus 1, Christensenellaceae R-7, Acetatifactor, Dubosiella, Parasutterella, Faecalibaculum, and Defluviitaleaceae UCG-011, in the progression of liver fibrosis and the therapeutic efficacy of AG. This investigation shows that during the process of AG ameliorating BDL-induced liver fibrosis, bile acid derivatives such as CDCA, TCDCA, 3-DHC, UCA, DCA, among others, play significant roles. In this study, we identified that several non-bile acid metabolites, such as Deltarasin, Thr-Ile-Arg, etc., are entailed in the process of AG improving liver fibrosis., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The biomass of Isodon rubescens stems is greater than that of the leaves. The stems possess a considerable surface area, although less than that of the leaves. The photosynthetic rates, light response curves and chlorophyll fluorescence characteristics of the stems were determined in this study to clarify their photosynthetic capacity and photosynthetic potential. The results showed that the I. rubescens stems possessed considerable photosynthetic capacity, although less than that of the leaves. The shape of the light response curve of the I. rubescens stem was different from that of leaf. The light response curve of stems slowly increased during the intermediate growth period. The light saturation point of the stems was significantly greater than that of the leaves. There was clear, strong light suppression in both stems and leaves. However, I. rubescens stems could effectively photosynthesize, and the stem has a high light saturation point and can adapt to intense light., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Cognitive decline and memory impairment are subsequently result in neuronal apoptosis and synaptic damage. Aberrant regulation of microRNAs has been implicated in the pathogenesis of Alzheimer's disease (AD) and may play a pivotal role in the early stages of the disease. In this study, we identified the critical role of miR-4763-3p in AD pathogenesis, focusing on early-stage mild cognitive impairment (AD-MCI). Leveraging fluorescence in situ hybridization, we observed miR-4763-3p upregulation in AD hippocampal tissue, colocalizing with Aβ and Tau. Antagomir-mediated inhibition of miR-4763-3p ameliorated cognitive decline in AD-MCI mice. RNA-seq and functional assays revealed that miR-4763-3p targets ATP11A, and antagomir enhancing inward flipping of the "eat me" phosphatidylserine signal on the surface of neuronal cells, autophagy, and clearance of Aβ/lipofuscin, while reducing neuroinflammation and neuronal apoptosis. Mechanistically, miR-4763-3p modulates the PI3K/AKT/mTOR/Bcl2 pathway, thereby promoting neuronal autophagy and reducing apoptotic crosstalk. These findings underscore miR-4763-3p as a therapeutic target for AD-MCI, offering a novel strategy to enhance neuronal autophagy, alleviate inflammation, and improve cognitive function., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)